Vitamins and Cancer: Is Nutrient Balance Important?
Recently in the American Journal of Clinical Nutrition, Wang and colleague published an article describing follow-up analyses of the high-dose vitamin E and C component of the Physicians Health Study II. This study was exceptional in that it recruited a large number of subjects that were well-nourished (male physicians), randomized them to various dietary supplements, and followed them to track key cardiovascular and cancer-related endpoints for a very long time: follow-up occurred over 14 years. However, some of the results were a little paradoxical. We explain further after going into a few details about the research.
The design of the study was rather complex. The researchers used a 2X2X2X2 factorial design, which resulted in 16 possible combinations of placebo and/or the four interventional products:
· A multivitamin (recommended amounts of essential vitamins and minerals)
· Vitamin C (500 mg ascorbic acid)
· Vitamin E (400 IU alpha-tocopherol)
· Beta-carotene (50 mg)
Back in 2009, researchers reported on the results of the high dose vitamin C and E intervention phase on the primary endpoints. They did not find a benefit to vitamins C and E over 7.6 years of intervention. In the most recent publication, the authors follow-up these results by looking to see whether there were any trends during another 2.8 years in which the subjects were followed but were no longer taking supplements. Once again, no difference was seen between the supplemented and placebo groups in either cancer diagnoses or cardiovascular disease. The authors looked at the data in many different ways and did not find significant effects in any sub-group or cancer type, with the exception of a marginally significant reduction in colorectal cancer diagnoses during the observational period of the study.
However, in 2012, the researchers that looked at the multivitamin component of the same study found a significant reduction in cancer incidence of around 8% after 10 years of supplementation. There was also a reduction in cancer mortality by 12% that was borderline significant.
This is important because the multivitamin formulation used in contained the Recommended Dietary Allowance (RDA) for both vitamins C and E for this age group (60 mg and 50 IU, respectively), along with RDAs for the other essential vitamins and minerals. It seems that while high doses of vitamins C and E have no effect on cancer incidence, using a multivitamin that contains the minimum amount of all necessary vitamins and minerals has a modestly protective effect when taken over a long period of time, even in a well-nourished and generally healthy population.
Recent articles that have been negative about the effects that multivitamins have on health. This study, which is possibly the longest intervention study conducted in over 10,000 subjects using dietary supplements, has shown that all-round good nutrition, provided in tablet form, is effective in modestly reducing cancer incidence in a population that is not undernourished. Balanced nutrition appear to be the key to a long and healthy life.
Lu Wang, Howard D Sesso, Robert J Glynn, William G Christen, Vadim Bubes, JoAnn E Manson, Julie E Buring, and J Michael Gaziano. Vitamin E and C supplementation and risk of cancer in men: posttrial follow-up in the Physicians’ Health Study II randomized trial. Am J Clin Nutr 2014 ajcn.085480; First published online July 9, 2014. doi:10.3945/ajcn.114.085480
Gaziano JM, Glynn RJ, Christen WG, Kurth T, Belanger C, MacFadyen J, Bubes V, Manson JE, Sesso HD, Buring JE. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2009 Jan 7;301(1):52-62. doi: 10.1001/jama.2008.862. Epub 2008 Dec 9. http://www.ncbi.nlm.nih.gov/pubmed/19066368
Gaziano JM, Sesso HD, Christen WG, Bubes V, Smith JP, MacFadyen J, Schvartz M, Manson JE, Glynn RJ, Buring JE. Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2012 Nov 14;308(18):1871-80. http://www.ncbi.nlm.nih.gov/pubmed/23162860